Voltage-gated Ca/2+ channels regulate cellular processes, such as the release of neurotransmitters from nerve terminals, essential for proper functioning of the nervous system. Specific classes of Ca/2+ channels are immobilized in presynaptic axon terminals where their activity is coupled to the exocytic release of neurotransmitters. How these Ca/2+ channels become localized to synaptic sites of action is largely unknown. Preliminary evidence suggests that neuronal Ca/2+ channels associate with members of a family of synapse associated proteins (SAPs) that are implicated in the clustering of ion channels at synapses. The studies outlined herein will test the hypothesis that presynaptic Ca/2+ channel localization depends on such interactions with SAPs. The relevance of the proposed studies lies in the possibility that these interactions may coordinate the functional architecture of the presynaptic membrane. Biochemical, immunocytochemical, and molecular biologic techniques will be used to characterize the molecular determinants and functional impact of SAP/Ca/2+ channel interactions with respect to presynaptic Ca/2+ channel localization in neurons. The goal of the proposed research is to gain insight into how neurons establish the functionally distinct micro-domains that underly synaptic transmission in the nervous system.